Abstract

We have investigated the role of erythroid transcription factors mRNA expression in
patients with acute myeloid leukemia (AML) in the context of cytogenetic and other
prognostic molecular markers, such as FMS-like Tyrosine Kinase 3 (FLT3), Nucleophosmin
1 (NPM1), and CCAAT/enhance-binding protein α (CEBPA) mutations. Further validation
of Erythroid Krüppel-like Factor (EKLF) mRNA expression as a prognostic factor was
assessed.

We evaluated GATA binding protein 1 (GATA1), GATA binding protein 2 (GATA2), EKLF
and Myeloproliferative Leukemia virus oncogen homology (cMPL) gene mRNA expression
in the bone marrow of 65 AML patients at diagnosis, and assessed any correlation with
NPM1, FLT3 and CEBPA mutations. EKLF-positive AML was associated with lower WBC in peripheral blood (P = 0.049), a higher percentage
of erythroblasts in bone marrow (p = 0.057), and secondary AMLs (P = 0.036). High
expression levels of EKLF showed a trend to association with T-cell antigen expression,
such as CD7 (P = 0.057). Patients expressing EKLF had longer Overall Survival (OS)
and Event Free Survival (EFS) than those patients not expressing EKLF (median OS was
35.61 months and 19.31 months, respectively, P = 0.0241; median EFS was 19.80 months
and 8.03 months, respectively, P = 0.0140). No correlation of GATA1, GATA2, EKLF and
cMPL levels was observed with FLT-3 or NPM1 mutation status. Four of four CEBPA mutated
AMLs were EKLF positive versus 10 of 29 CEBPA wild-type AMLs; three of the CEBPA mutated,
EKLF-positive AMLs were also GATA2 positive. There were no cases of CEBPA mutations
in the EKLF-negative AML group. In conclusion, we have validated EKLF mRNA expression
as an independent predictor of outcome in AML, and its expression is not associated
with FLT3-ITD and NPM1 mutations. EKLF mRNA expression in AML patients may correlate
with dysregulated CEBPA.